Development of an operational productivity tool within a cancer treatment center pharmacy.

PURPOSE: The development and implementation of an operational productivity tool in an academic cancer treatment center are described. SUMMARY: Based on the increasing complexity of care delivery within the oncology setting, solutions were explored within Cleveland Clinic pharmacy's productivity model. Data were electronically captured based on orders processed through the outpatient oncology setting, including hazardous and nonhazardous medications. Based on current workflow, inpatient and outpatient orders were reviewed in productivity metrics. The metric defining the variability of the workload itself was weighted dispense type as it was the best representation of a mixed-skill workflow. After conducting workflow process mapping, discrete measurable steps were assessed and evaluated daily. Operational components of interest included pharmacist verification activities and technician compounding activities. Historical production data were sampled for assigning relative value units (RVUs) respective to time to normalize workload into a common unit (i.e., 1 hour) and to relate work demand in a highly variable setting. RVUs were assigned and delineated by cognitive and distributive activities for pharmacists and technicians, respectively. The Cleveland Clinic department of pharmacy developed a productivity tool to retrospectively measure workload involving time to review, verify, reconstitute, admix, and deliver chemotherapeutic agents. The weighting of each medication allowed for precise and meaningful evaluation of productivity. With RVUs assigned to 2 years of operational metrics, there now exists an opportunity to monitor performance trends within the cancer treatment center pharmacy. The data are readily retrievable within the electronic health record. CONCLUSION: The productivity data provided precise information to assess trends in operations within the pharmacy of an outpatient cancer treatment center.

Predator-based psychosocial stress model of PTSD differentially influences voluntary ethanol consumption depending on methodology.

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder typified by diagnostic symptom clusters including hyperarousal, avoidance, negative cognitions and mood, and intrusive re-experiencing of the traumatic event. Patients with PTSD have been reported to self-medicate with alcohol to ameliorate hyperarousal symptoms associated with the disorder. Research utilizing rodent models of PTSD to emulate this behavioral phenomenon has thus far yielded inconsistent results. In the present study, we examined the effects of a predator-based psychosocial stress model of PTSD on voluntary ethanol consumption. In the first of two experiments, following exposure to a 31-day stress or control paradigm, rats were singly housed during the dark cycle with free access to 1% sucrose solution or 10% ethanol, which was also sweetened with 1% sucrose. Over the course of a 20-day period of ethanol access, stressed rats consumed significantly less ethanol than non-stressed rats. These counterintuitive results prompted the completion of a second experiment which was identical to the first, except rats were also exposed to the two-bottle paradigm for 20 days before the stress or control paradigm. In the second experiment, after the stress manipulation, stressed rats exhibited significantly greater ethanol preference than non-stressed rats. These findings suggest that prior exposure to ethanol influences the subsequent effect of stress on ethanol intake. They also validate the use of the present model of PTSD to examine potential mechanisms underlying stress-related changes in ethanol-seeking behavior.

Evolution of Multidisciplinary Translational Teams (MTTs): Insights for Accelerating Translational Innovations.

There is growing consensus about the factors critical for development and productivity of multidisciplinary teams, but few studies have evaluated their longitudinal changes. We present a longitudinal study of 10 multidisciplinary translational teams (MTTs), based on team process and outcome measures, evaluated before and after 3 years of CTSA collaboration. Using a mixed methods approach, an expert panel of five judges (familiar with the progress of the teams) independently rated team performance based on four process and four outcome measures, and achieved a rating consensus. Although all teams made progress in translational domains, other process and outcome measures were highly variable. The trajectory profiles identified four categories of team performance. Objective bibliometric analysis of CTSA-supported MTTs with positive growth in process scores showed that these teams tended to have enhanced scientific outcomes and published in new scientific domains, indicating the conduct of innovative science. Case exemplars revealed that MTTs that experienced growth in both process and outcome evaluative criteria also experienced greater innovation, defined as publications in different areas of science. Of the eight evaluative criteria, leadership-related behaviors were the most resistant to the interventions introduced. Well-managed MTTs demonstrate objective productivity and facilitate innovation.

Central nervous system influences in asthma.

Asthma is a biomedical disorder whose presentation can be markedly influenced by neurological and psychological factors. This chapter describes several approaches that provide insight into the role of psychological factors and brain function in asthma. These include the study of placebo responses and recent explorations using functional neuroimaging during the onset of asthma symptoms. Although the specific mechanisms involved remain uncertain, we are gaining an appreciation for some of the neurocircuitry that is involved. The insula and ACC may modulate inflammatory processes by their influence on neuroendocrine responses to stress, including highly studied effects on the HPA axis and its physiologic responses. However much we have recently learned, it is clear that further study of this topic is critical to fully explicate the role of the brain in asthma.

Assessing and evaluating multidisciplinary translational teams: a mixed methods approach.

A case report illustrates how multidisciplinary translational teams can be assessed using outcome, process, and developmental types of evaluation using a mixed-methods approach. Types of evaluation appropriate for teams are considered in relation to relevant research questions and assessment methods. Logic models are applied to scientific projects and team development to inform choices between methods within a mixed-methods design. Use of an expert panel is reviewed, culminating in consensus ratings of 11 multidisciplinary teams and a final evaluation within a team-type taxonomy. Based on team maturation and scientific progress, teams were designated as (a) early in development, (b) traditional, (c) process focused, or (d) exemplary. Lessons learned from data reduction, use of mixed methods, and use of expert panels are explored.

The rebirth of neuroscience in psychosomatic medicine, Part II: clinical applications and implications for research.

During the second half of the last century, biopsychosocial research in psychosomatic medicine largely ignored the brain. Neuroscience has started to make a comeback in psychosomatic medicine research and promises to advance the field in important ways. In this paper we briefly review select brain imaging research findings in psychosomatic medicine in four key areas: cardiovascular regulation, visceral pain in the context of functional gastrointestinal disorders, acute and chronic somatic pain and placebo. In each area, there is a growing literature that is beginning to define a network of brain areas that participate in the functions in question. Evidence to date suggests that cortical and subcortical areas that are involved in emotion and emotion regulation play an important role in each domain. Neuroscientific research is therefore validating findings from previous psychosomatic research and has the potential to extend knowledge by delineating the biological mechanisms that link mind and body more completely and with greater specificity. We conclude with a discussion of the implications of this work for how research in psychosomatic medicine is conducted, the ways in which neuroscientific advances can lead to new clinical applications in psychosomatic contexts, the implications of this work for the field of medicine more generally, and the priorities for research in the next 5 to 10 years.

The rebirth of neuroscience in psychosomatic medicine, Part I: historical context, methods, and relevant basic science.

Neuroscience was an integral part of psychosomatic medicine at its inception in the early 20th century. Since the mid-20th century, however, psychosomatic research has largely ignored the brain. The field of neuroscience has burgeoned in recent years largely because a variety of powerful new methods have become available. Many of these methods allow for the noninvasive study of the living human brain and thus are potentially available for integration into psychosomatic medicine research at this time. In this first paper we examine various methods available for human neuroscientific investigation and discuss their relative strengths and weaknesses. We next review some basic functional neuroanatomy involving structures that are increasingly being identified as relevant for psychosomatic processes. We then discuss, and provide examples of, how the brain influences end organs through "information transfer systems," including the autonomic, neuroendocrine, and immune systems. The evidence currently available suggests that neuroscience holds great promise for advancing the goal of understanding the mechanisms by which psychosocial variables influence physical disease outcomes. An increased focus on such mechanistic research in psychosomatic medicine is needed to further its acceptance into the field of medicine.

Social regulation of gene expression in human leukocytes.

BACKGROUND: Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. RESULTS: DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-kappaB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways. CONCLUSION: These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.

Placebo response in asthma: a robust and objective phenomenon.

BACKGROUND: Placebos are hypothesized to exert positive effects on medical conditions by enhancing patient expectancies. Recent reviews suggest that placebo benefits are restricted to subjective responses, like pain, but might be ineffective for objective physiologic outcomes. Nevertheless, mind-body links and placebo responsivity in asthma are widely believed to exist. OBJECTIVE: We carried out a randomized, double-blind investigation to (1) determine whether placebo can suppress airway hyperreactivity in asthmatic subjects, (2) quantify the placebo effect, (3) identify predictors of the placebo response, and (4) determine whether physician interventions modify the placebo response. METHODS: In a double-blind, crossover design investigation, 55 subjects with mild intermittent and persistent asthma with stable airway hyperreactivity were randomized to placebo or salmeterol before serial methacholine challenges. Subjects were additionally randomized to physician interactions that communicated either positive or neutral expectancies regarding drug effect. RESULTS: Placebo bronchodilator administration significantly reduced bronchial hyperreactivity compared with baseline (the calculated concentration of methacholine required to induce a 20% decrease in FEV(1) nearly doubled); 18% of subjects were placebo responders by using conservative definitions. Experimental manipulation of physician behavior altered perceptions of the physician but not the magnitude or frequency of the placebo response. CONCLUSIONS: Objective placebo effects exist in asthma. These responses are of significant magnitude and likely to be meaningful clinically. The placebo response was not modulated by alterations in physician behavior in this study. CLINICAL IMPLICATIONS: The placebo response in patients with asthma is important in understanding the limitations of clinical research studies and in maximizing safe and effective therapies. This article confirms the existence of a strong placebo response in an objective and clinically relevant measure of disease activity.

Altering expectancy dampens neural response to aversive taste in primary taste cortex.

The primary taste cortex consists of the insula and operculum. Previous work has indicated that neurons in the primary taste cortex respond solely to sensory input from taste receptors and lingual somatosensory receptors. Using functional magnetic resonance imaging, we show here that expectancy modulates these neural responses in humans. When subjects were led to believe that a highly aversive bitter taste would be less distasteful than it actually was, they reported it to be less aversive than when they had accurate information about the taste and, moreover, the primary taste cortex was less strongly activated. In addition, the activation of the right insula and operculum tracked online ratings of the aversiveness for each taste. Such expectancy-driven modulation of primary sensory cortex may affect perceptions of external events.

Cardiovascular reactivity to work stress predicts subsequent onset of hypertension: the Air Traffic Controller Health Change Study.

OBJECTIVE: The hypothesis that increased blood pressure reactivity to stress is an early risk marker of hypertension was tested in a 1994 follow-up of the 1974 to 1978 Air Traffic Controller Health Change Study sample. METHODS: Assessments in 1974 to 1978 included physical examinations and recordings (every 20 minutes for 5 hours) of both workload (planes within controller airspace) and blood pressure reactivity. Individual differences in reactivity were used to predict 1994 self-report of ever having been told by a physician to take antihypertensive medication, assessed in a telephone survey of 218 respondents who were normotensive or stage 1 hypertensive in 1974 to 1978. RESULTS: Each SD increase in baseline systolic reactivity was associated with a 1.7 (p <.019) increase in the relative-odds of 1994 hypertension, after controlling for age, body mass index, and clinic systolic and diastolic blood pressure at clinical examination, with effects comparable for baseline normotensives and stage 1 hypertensives. CONCLUSION: A 20-year follow-up of originally normotensive and stage I hypertensive workers suggests that increased systolic blood pressure reactivity to work stress is associated with long-term risk of hypertension.

Placebo-induced changes in FMRI in the anticipation and experience of pain.

The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.